Project Summary/Abstract Pain after surgical incision is a common clinical problem. For many patients, postoperative pain is poorly controlled despite treatment with conventional therapeutics. We hypothesize that incision increases post- operative pain in sensory afferents via changes in expression and function of voltage-gated sodium channels (Nav). We plan to develop and validate a new model of acute post laminectomy pain that will allow for clinically relevant pain behaviors to be identified. These pain behaviors will be validated using three distinct analgesic techniques previously shown to have clinical relevance. Our translational approach includes molecular biology and functional neuronal imaging (Na+ and Ca+2 imaging). These techniques will serve to further the training and education of the applicant. Results from this proposed research will advance this area of investigation, and contribute to future funding for the applicant as an independent clinician-scientist. This work will provide much needed information for future development of novel analgesics that are devoid of serious side effects, enabling physicians to provide better perioperative care to surgical patients. PUBLIC HEALTH RELEVANCE: Over 1.2 million spine surgeries are performed in the U.S. each year. Half of those patients will have inadequate pain relief in the perioperative period. Our current treatments for postoperative pain have limited efficacy and serious side effects;a problem that leads to increased morbidity, mortality, and healthcare costs. In order to provide better post surgical pain control for the expanding population, we need to understand mechanisms of nociception after surgical incision. These studies will be the first to address voltage gated sodium channels in a clinically relevant model of acute post laminectomy pain.